Neuroinflammation associated with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may facilitate seizures. We previously showed that intraventricular administration of cerebrospinal fluid from patients with anti-NMDAR encephalitis to mice precipitates seizures, thereby confirming that antibodies are directly pathogenic. To determine whether interleukin (IL)-1-mediated inflammation exacerbates autoimmune seizures, we asked whether blocking the effects of IL-1 by anakinra, a selective IL-1 receptor antagonist, blunts antibody-induced seizures.
We infused C57BL/6 mice intraventricularly with purified serum IgG from patients with anti-NMDAR encephalitis or monoclonal anti-NMDAR IgG; subdural electroencephalogram was continuously recorded. After a 6-day interval, mice received anakinra (25mg/kg sc, twice daily) or vehicle for 5 days. Following a 4-day washout period, we performed behavioral tests to assess motor function, anxiety, and memory, followed by hippocampus tissue analysis to assess astrocyticrapeutic effects of anakinra in other severe autoimmune and inflammatory seizure syndromes. Targeting inflammation via blocking IL-1 receptor-mediated signaling may be promising for developing novel treatments for refractory autoimmune seizures.
Our evidence supports a role for IL-1 in the pathogenesis of seizures in anti-NMDAR encephalitis. These data are consistent with therapeutic effects of anakinra in other severe autoimmune and inflammatory seizure syndromes. Targeting inflammation via blocking IL-1 receptor-mediated signaling may be promising for developing novel treatments for refractory autoimmune seizures.Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but it can also disrupt verbal fluency with significant costs to quality of life. The current study investigated how variability of bilateral active electrode coordinates along the superior/inferior, anterior/posterior, and lateral/medial axes in the subthalamic nucleus (STN) or the globus pallidus interna (GPi) contribute to changes in verbal fluency. We predicted that electrode location in the left hemisphere would be linked to changes in fluency, especially in the STN.
Forty PD participants treated with bilateral DBS targeting STN (n=23) or GPi (n=17) completed verbal fluency testing in their optimally treated state before and after DBS therapy. Normalized atlas coordinates from left and right active electrode positions along superior/inferior, anterior/posterior, and lateral/medial axes were used to predict changes in fluency postoperatively, separately for patients with STN and GPi targets.
Consistent with prior studies, fluency significantly declined pre- to postsurgery (in both DBS targets). In STN-DBS patients, electrode position along the inferior to superior axis in the left STN was a significant predictor of fluency changes; relatively more superior left active electrode was associated with the largest fluency declines in STN. Electrode coordinates in right STN or GPi (left or right) did not predict fluency changes.
We discuss these findings in light of putative mechanisms and potential clinical impact.
We discuss these findings in light of putative mechanisms and potential clinical impact.The objective of the current study was to define trends in postoperative surveillance imaging following liver-directed treatment of hepatocellular carcinoma (HCC), and characterize the impact of high-intensity surveillance on long-term survival.
Patients who underwent liver- directed therapy for HCC between 2004 and 2016 were identified using the SEER-Medicare database. Trends in surveillance intensity over time, factors associated with high surveillance intensity and the impact of surveillance on long-term outcomes were examined.
Utilization of high-intensity surveillance abdominal imaging (?6 scans over 2 years) following liver-directed therapy of HCC decreased over time (2004-2007 n?=?130, 36.1% vs. 2008-2011 n?=?181, 29.5% vs. https://www.selleckchem.com/products/ml324.html 2012-2016 n?=?111, 24.5%; p?&lt;?0.001). History of chronic viral hepatitis (hepatitis B odds ratio [OR], 1.98; 95% confidence interval [CI] 1.15-3.43; hepatitis C OR, 1.79; 95% CI 1.32-2.43), presence of regional (vs. local-only) disease (OR, 1.47; 95% CI 1.09-1.98) and receipt of transplantation (OR, 2.23; 95% CI 1.57-3.17) were associated with higher odds of high intensity surveillance. Intensity of surveillance imaging was not associated with long-term survival (5-year overall survival low-intensity, 48.1% vs. high-intensity, 48.9%; hazards ratio, 0.94; 95% CI 0.78-1.13).
Utilization of posttreatment surveillance imaging decreased over time following liver-directed therapy for HCC. While utilization of high-intensity screening varied by HCC procedure performed, intensity of surveillance had no effect on survival.
Utilization of posttreatment surveillance imaging decreased over time following liver-directed therapy for HCC. While utilization of high-intensity screening varied by HCC procedure performed, intensity of surveillance had no effect on survival.Stereotactic radiosurgery (SRS) is rapidly becoming the standard of care for many intracranial targets. The characteristics of the planning target volume (PTV) can affect the intermediate dose spill and thus normal brain volume dose which is correlated with brain toxicity. R50% (volume receiving 50% of prescription dose divided by PTV volume) is a useful metric to quantify the intermediate dose spill. We propose a novel understanding of how the PTV surface area (SA) affects the intermediate dose spill of SRS treatments.
Using a phantom model provided by a computed tomography (CT) of the IROC Head Phantom® and Eclipse® Treatment Planning System, we investigate the relationship of R50% and SAin single-target SRS treatments. The planning studies are conducted for SRS treatments on a Varian TrueBeam® linear accelerator with high-definition MLC and a 6MVFFF beam mode. These data are analyzed to ascertain trends in R50% related to SA. Since SAis not available as a structure property in the Eclipse RR50%Analytic prediction model. The predicted value of R50%Analytic for a given PTV could be used for guidance during SRS treatment plan optimization, and plan evaluation for that PTV.